Gestational diabetes is driven by microbiota-induced inflammation months before diagnosis.

OBJECTIVE: Gestational diabetes mellitus (GDM) is a condition in which women without diabetes are diagnosed with glucose intolerance during pregnancy, typically in the second or third trimester. Early diagnosis, along with a better understanding of its pathophysiology during the first trimester of pregnancy, may be effective in reducing incidence and associated short-term and long-term morbidities. DESIGN: We comprehensively profiled the gut microbiome, metabolome, inflammatory cytokines, nutrition and clinical records of 394 women during the first trimester of pregnancy, before GDM diagnosis. We then built a model that can predict GDM onset weeks before it is typically diagnosed. Further, we demonstrated the role of the microbiome in disease using faecal microbiota transplant (FMT) of first trimester samples from pregnant women across three unique cohorts. RESULTS: We found elevated levels of proinflammatory cytokines in women who later developed GDM, decreased faecal short-chain fatty acids and altered microbiome. We next confirmed that differences in GDM-associated microbial composition during the first trimester drove inflammation and insulin resistance more than 10 weeks prior to GDM diagnosis using FMT experiments. Following these observations, we used a machine learning approach to predict GDM based on first trimester clinical, microbial and inflammatory markers with high accuracy. CONCLUSION: GDM onset can be identified in the first trimester of pregnancy, earlier than currently accepted. Furthermore, the gut microbiome appears to play a role in inflammation-induced GDM pathogenesis, with interleukin-6 as a potential contributor to pathogenesis. Potential GDM markers, including microbiota, can serve as targets for early diagnostics and therapeutic intervention leading to prevention.

Revised Protocol for Secondary Prevention of Congenital Cytomegalovirus Infection With Valaciclovir Following Infection in Early Pregnancy.

BACKGROUND: A previous randomized placebo-controlled study found valaciclovir to be effective in reducing the rate of vertical cytomegalovirus transmission from mother to fetus. The better results in women infected in the first trimester compared to the periconception period were attributed to the timing of treatment. The aim of the present study was to evaluate valaciclovir efficacy in this setting using a revised protocol. METHODS: All pregnant women treated with valaciclovir in 2020-2022 who met the same criteria as in the original study were identified retrospectively from the database of the same medical center. Treatment, however, was initiated earlier: up to 9 weeks or 8 weeks from the presumed time of infection in women infected in the periconception period or the first trimester, respectively. The primary endpoint was rate of vertical cytomegalovirus transmission. Results were compared with the placebo arm in the previous study. RESULTS: Among 178 women who completed valaciclovir treatment, amniocentesis was positive for cytomegalovirus in 14 women (7.9%), significantly (P < .001) lower compared with 14 of 47 (30%) in the placebo arm in the previous study. The proportion of positive amniocentesis in the valaciclovir was significantly lower than the placebo arm both among women infected in the first trimester (14/119 vs 11/23; odds ratio [OR] = 0.15; 95% confidence interval [CI]: .05-.45, P < .001), as well as among those infected in the periconception period (0/59 vs 3/24, OR = 0; 95% CI 0-.97, P = .02). CONCLUSIONS: This study provides further evidence of the efficacy of valaciclovir in preventing vertical transmission of cytomegalovirus after primary maternal infection. Efficacy is improved with earlier treatment.

Valaciclovir to prevent vertical transmission of cytomegalovirus after maternal primary infection during pregnancy: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Cytomegalovirus is a common congenital infection, with high morbidity after an early primary maternal infection. No effective means exist to prevent viral transmission to the fetus. We aimed to investigate whether valaciclovir can prevent vertical transmission of cytomegalovirus to the fetus in pregnant women with a primary infection acquired early in pregnancy. METHODS: This prospective, randomised, double-blind, placebo-controlled trial was done at the Infectious Feto-Maternal Clinic of Rabin Medical Center (Petach Tikvah, Israel). Pregnant women aged 18 years or older, with serological evidence of a primary cytomegalovirus infection acquired either periconceptionally or during the first trimester of pregnancy, were randomly assigned to oral valaciclovir (8 g per day, twice daily) or placebo from enrolment until amniocentesis at 21 or 22 gestational weeks. Randomisation was done separately for participants infected periconceptionally or during the first trimester and was done in blocks of four. Patients and researchers were masked to participant allocation throughout the entire study period. The primary endpoint was the rate of vertical transmission of cytomegalovirus. Statistical analyses were done according to per-protocol principles. The study was registered at ClinicalTrials.gov, NCT02351102. FINDINGS: Between Nov 15, 2015, and Oct 8, 2018, we enrolled and randomly assigned 100 patients to receive valaciclovir or placebo. Ten patients were excluded, five from each study group; therefore, the final analysis included 45 patients (all singletons) in the valaciclovir group and 45 patients (43 singletons and two sets of twins) in the placebo group. In the valaciclovir group, including both first trimester and periconceptional infections, five (11%) of 45 amniocenteses were positive for cytomegalovirus, compared with 14 (30%) of 47 amniocenteses in the placebo group (p=0·027; odds ratio 0·29, 95% CI 0·09-0·90 for vertical cytomegalovirus transmission). Among participants with a primary cytomegalovirus infection during the first trimester, a positive amniocentesis for cytomegalovirus was significantly less likely in the valaciclovir group (two [11%] of 19 amniocenteses) compared with the placebo group (11 [48%] of 23 amniocenteses; p=0·020. No clinically significant adverse events were reported. INTERPRETATION: Valaciclovir is effective in reducing the rate of fetal cytomegalovirus infection after maternal primary infection acquired early in pregnancy. Early treatment of pregnant women with primary infection might prevent termination of pregnancies or delivery of infants with congenital cytomegalovirus. FUNDING: None.

The association between maternal cytomegalovirus urinary excretion and congenital infection rate.

BACKGROUND: In utero Cytomegalovirus (CMV) vertical transmission occurs predominantly during primary maternal infection. There are no known non-invasive methods for diagnosis of fetal infection before delivery, however some risk factors have been suggested. We aimed to evaluate the association between maternal CMV urinary excretion and congenital CMV infection. METHODS: A retrospective cohort study of all women who were diagnosed with primary CMV infection during pregnancy in a single university affiliated tertiary medical center, between 2012 and 2016. We examined congenital CMV infection and disease rates among infants born to women with and without CMV urinary excretion. RESULTS: Overall, 126 women were included, 77 in the positive urinary excretion group, and 49 in the negative urinary excretion group. There was no difference in maternal symptoms between the groups. We found no difference in congenital CMV infection and disease rates between infants born to women with and without urinary excretion of CMV (congenital infection rate 37.1% vs. 24.4%, p = 0.209, congenital disease rate of 18.2% vs. 22.4%, p = 0.648). Women with positive urinary CMV excretion had lower IgG avidity values (36.7% vs 54.6%, p = 0.007), with no additional difference in serology pattern. Compared to asymptomatic women, those with CMV related symptoms did not have significantly higher rates of urinary excretion of CMV (70% vs. 60.5%, p = 0.38) or congenital infection rates (40.7% vs. 31.2%, p = 0.48). CONCLUSION: Among infants of women with primary CMV infection in pregnancy, we did not find an association between urinary excretion of CMV and congenital CMV infection.

Women's preferences for mode of second birth-A prospective study of two Israeli birth cohorts.

INTRODUCTION: Various biopsychosocial factors affect women's preferences with respect to mode of birth, but they are usually not examined simultaneously and prospectively. In the current study, we assessed the contribution of personal characteristics of first-time mothers, their prior prenatal perceptions, events during birth, and subjective birth experiences, on their preference about mode of second birth. METHODS: This was a secondary analysis of two prospective birth cohort studies. Participants included 832 primiparous women recruited mostly from women's health centers in Israel, and through natural birth communities and cesarean birth websites. Women completed questionnaires prenatally and were followed up at 6-8 weeks postpartum to understand their preferences for a second birth. RESULTS: Regression models indicated that after vaginal first birth, being less religious, believing that birth is a medical process, and having a negative experience increased the odds of preferring primary cesarean for the second birth. After cesarean birth, being more religious, having higher education, conceiving spontaneously, having a more negative birth experience, and perceiving better treatment from the staff during birth contributed to preferring vaginal birth for the second birth. CONCLUSIONS: Religiosity is central to women's preferences, probably because of its association with the desire to have many children. Modifiable factors, such as women's beliefs about the nature of birth, their overall birth experience, and their perceived treatment from the staff, could influence the uptake of having vaginal births. Intrapartum care that is empathic and encouraging, along with education about modes of birth, could help decrease cesarean birth rates.

Second Trimester Biochemical Markers as Possible Predictors of Pathological Placentation: A Retrospective Case-Control Study.

OBJECTIVE: We aimed to evaluate the association between second trimester biochemical markers and pathological placentation. METHODS: This was a retrospective case-control study (2007-2014) of singleton gestations at a university-affiliated tertiary center. Women with pathologic placentation were subdivided into three groups: placenta accreta (group A), placenta previa (group B), or both (group C). We compared second trimester biochemical screening markers taken between 16 + 0 and 19 + 6 weeks of gestation between groups A, B, and C, and women with normal placentation (group D). Obstetrical and neonatal outcomes, risk factors for pathologic placentation, and second trimester biochemical marker values were compared between groups. RESULTS: Overall, 301 deliveries were evaluated: 64 (21%) in group A, 66 (22%) in group B, 17 (6%) in group C, and 153 (51%) in group D. Each of the pathological placentation groups individually had a higher median alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) multiples of median (MoM) than the controls, with the highest values of AFP and hCG observed among women with placenta accreta and the lowest values among the controls. When a multivariant analysis was applied, the hCG levels remained significantly correlated with pathological placentation. Receiver operation characteristic curves for AFP, hCG, or both were computed. For AFP the area under the ROC curve (AUC) was 0.573 (95% CI 0.515-0.630, p < 0.0274) and a cut-off value above 0.99 MoM demonstrated a sensitivity and specificity of 71 and 46%, respectively, for the prediction of pathological placentation. For hCG, the AUC was 0.662 (95% CI 0.605-0.715, p < 0.0001) and a cut-off value of 1.25 MoM demonstrated a sensitivity and specificity of 53 and 68%. When both markers were plotted, the AUC was 0.668 (95% CI 0.611-0.721, p < 0.0001) and sensitivity and specificity were 63 and 64%, respectively. A percentile MoM cut-off approach distinguished between two groups: a high-risk group (patients with AFP or hCG or both above the 75th percentile, odds ratio (OR) for pathological placentation 2.27, 95% CI 1.42-3.63), and a low-risk group (patients with AFP or hCG or both below the 25th percentile, OR for pathological placentation 0.38, 95% CI 0.24-0.60). CONCLUSION: Second trimester biomarkers such as hCG and AFP can be used to raise a suspicion towards characterizing women into high-risk and low-risk groups for pathological placentation.

Testing a biopsychosocial model of the basic birth beliefs.

BACKGROUND: Women perceive what birth is even before they are pregnant for the first time. Part of this conceptualization is the basic belief about birth as a medical and natural process. These two separate beliefs are pivotal in the decision-making process about labor and birth. Adapting Engel's biopsychosocial framework, we explored the importance of a wide range of factors which may contribute to these beliefs among first-time mothers. METHOD: This observational study included 413 primiparae ≥24 weeks' gestation, recruited in medical centers and in natural birth communities in Israel. The women completed a questionnaire which included the Birth Beliefs Scale and a variety of biopsychosocial characteristics such as obstetric history, birth environment, optimism, health-related anxiety, and maternal expectations. RESULTS: Psychological dispositions were more related to the birth beliefs than the social or biomedical factors. Sociodemographic characteristics and birth environment were only marginally related to the birth beliefs. The basic belief that birth is a natural process was positively related to optimism and to conceiving spontaneously. Beliefs that birth is a medical process were related to pessimism, health-related anxiety, and to expectations that an infant's behavior reflects mothering. Expectations about motherhood as being naturally fulfilling were positively related to both beliefs. CONCLUSION: Psychological factors seem to be most influential in the conceptualization of the beliefs. It is important to recognize how women interpret the messages they receive about birth which, together with their obstetric experience, shape their beliefs. Future studies are recommended to understand the evolution of these beliefs, especially within diverse cultures.

Symptomatic congenital cytomegalovirus disease following non-primary maternal infection: a retrospective cohort study.

BACKGROUND: Scarce data exist about screening, diagnosis and prognosis of non-primary Cytomegalovirus (CMV) during pregnancy. We aimed to examine antenatal diagnosis of maternal non-primary CMV infection and to identify risk factors for congenial CMV disease. METHODS: Retrospective cohort of 107 neonates with congenital symptomatic CMV infection, following either primary (n = 95) or non-primary (n = 12) maternal CMV infection. We compared the groups for the manifestations and severity of congenial CMV disease, as well as for possible factors associated with the risk of developing CMV related infant morbidity. RESULTS: Disease severity is not similar in affected newborns, with a higher incidence of abnormal brain sonographic findings, following primary versus non-primary maternal CMV infection (76.8% vs. 8.3%, p < .001). Symptomatic congenital CMV disease following a non-primary infection is more frequent if gestational hypertensive disorders and/or gestational diabetes mellitus have ensued during pregnancy (33.3% vs. 9.9%, p <0.038), as well as if any medications were taken throughout gestation (50% vs. 16.8%, p <0.016). CMV-IgM demonstrates a low detection rate for non-primary maternal infection during pregnancy compared to primary infection (25% vs. 75.8%, p = 0.0008). CONCLUSION: Non-primary maternal CMV infection has an impact on the neonate. Although not readily diagnosed during pregnancy, knowledge of risk factors may aid in raising clinical suspicion.

Clinical Implications for Children Born With Congenital Cytomegalovirus Infection Following a Negative Amniocentesis.

BACKGROUND: Recently, congenital cytomegalovirus (cCMV) infection was reported irrespective of a negative amniotic fluid prenatal analysis for cytomegalovirus (CMV). The question of whether this phenomenon represents low sensitivity of the test or late development of fetal infection (after amniocentesis) was discussed, but not answered. However, if late transmission is the rule, then infants born with cCMV after negative amniocentesis would be expected to carry better prognosis than those who tested positive. METHODS: Data of all infants with cCMV infection, followed in 2 pediatric centers from 2006 to 2015, were reviewed. Infant outcome after birth of symptomatic vs asymptomatic disease was compared with infants born after a negative amniocentesis (study group) and those with a positive amniocentesis (control group). RESULTS: Amniocentesis was performed in 301 pregnancies of our cohort of infants with cCMV and was negative for CMV in 47 (15.6%). There were fewer symptomatic cCMV neonates in the study group than in the control group (4.3% vs 25%; P < .001). Hearing impairment at birth was also less frequent in the study group (2.2% vs 17.4%; P = .012). None of the children in the study group had neurologic sequelae at long-term follow up, compared with 13 (14.1%) in the control group (P < .001). CONCLUSIONS: Although negative amniocentesis does not exclude cCMV, infants with cCMV born after a negative amniocentesis seldom present with mild clinical symptoms or cerebral ultrasound features at birth. These children also have a very good long-term outcome. Our findings support the theory of a late development of fetal infection, after the time of the amniocentesis.

Antenatal risk factors for symptomatic congenital CMV disease following primary maternal CMV infection.

OBJECTIVES: This study aimed to evaluate antenatal risk factors associated with symptomatic congenital cytomegalovirus (CMV) disease, following in utero vertical infection. METHODS: This study included a retrospective cohort of 155 neonates with congenital CMV infection, following primary maternal CMV infection during pregnancy, and were divided to symptomatic (n=95) and asymptomatic (n=60) newborns. RESULTS: Young maternal age (29.1±5.12 vs. 31.6±5.36 years, P=0.005), high risk occupation for viral exposure (20.0% vs. 11.7%, P=0.04), CMV IgG seroconversion at diagnosis (83.1% vs. 63.3%, P=0.005) and abnormal fetal MRI (11.6% vs. 0%, P=0.003) were found to be prognostic risk factors associated with symptomatic CMV disease of the newborn. Maternal febrile illness at diagnosis, IgG avidity, US findings and the timing of maternal infection were not associated with the occurrence of neonatal symptoms. CONCLUSIONS: Knowledge of the reported risk factors may assist in counseling parents with intra uterine CMV infection.

Lenticulostriated vasculopathy is a high-risk marker for hearing loss in congenital cytomegalovirus infections.

AIM: This study investigated the relationship between lenticulostriated vasculopathy (LSV) and hearing loss in 141 infants with congenital cytomegalovirus (cCMV) infection. METHODS: We included all infants with cCMV infection who were followed in our clinic for more than a year with only LSV signs of brain involvement on initial brain ultrasound. Group one comprised 13 infants with no hearing impairment at birth who were not treated with gan/valganciclovir during 2006-2009. Group two was 51 infants with LSV and no hearing impairment who had been treated since mid-2009. Group three was 25 infants born with LSV and hearing loss, who had been treated from birth. Group four was 52 control infants born during the same period with asymptomatic cCMV. Hearing tests were performed during the neonatal period and every four to six months until four years of age. RESULTS: Hearing deterioration was more extensive in group one (85%) than in group two (0%, p < 0.001) and the asymptomatic group (10%, p < 0.001) and occurred more often in group four (10%) than in group two (0%, p = 0.008). CONCLUSION: Lenticulostriated vasculopathy was common in infants with cCMV infection and may serve as a sign of central nervous system involvement and further hearing deterioration. Antiviral treatment may be prudent in such infants.

"Residential greenness, gestational diabetes mellitus (GDM) and microbiome diversity during pregnancy".

BACKGROUND: Gestational diabetes mellitus (GDM) is associated with reduced gut microbiota richness that was also reported to differ significantly between those living in rural compared to urban environments. Therefore, our aim was to examine the associations between greenness and maternal blood glucose levels and GDM, with microbiome diversity as a possible mediator in these associations. METHODS: Pregnant women were recruited between January 2016 and October 2017. Residential greenness was evaluated as mean Normalized Difference Vegetation Index (NDVI) within 100, 300 and 500 m buffers surrounding each maternal residential address. Maternal glucose levels were measured at 24-28 weeks of gestation and GDM was diagnosed. We estimated the associations between greenness and glucose levels and GDM using generalized linear models, adjusting for socioeconomic status and season at last menstrual period. Using causal mediation analysis, the mediation effects of four different indices of microbiome alpha diversity in first trimester stool and saliva samples were assessed. RESULTS: Of 269 pregnant women, 27 participants (10.04%) were diagnosed with GDM. Although not statistically significant, adjusted exposure to medium tertile levels of mean NDVI at 300 m buffer had lower odds of GDM (OR = 0.45, 95% CI: 0.16, 1.26, p = 0.13) and decreased change in mean glucose levels (ß = -6.28, 95% CI: 14.91, 2.24, p = 0.15) compared to the lowest tertile levels of mean NDVI. Mixed results were observed at 100 and 500 m buffers, and when comparing highest tertile levels to lowest. No mediation effect of first trimester microbiome on the association between residential greenness and GDM was observed, and a small, possibly incidental, mediation effect on glucose levels was observed. CONCLUSION: Our study suggests possible associations between residential greenness and glucose intolerance and risk of GDM, though without sufficient evidence. Microbiome in the first trimester, while involved in GDM etiology, is not a mediator in these associations. Future studies in larger populations should further examine these associations.

Expectant management of preterm premature rupture of membranes: is it all about gestational age?

OBJECTIVE: We sought to compare neonatal outcome in cases of uncomplicated preterm premature rupture of membranes (PPROM) (ie, no evidence of clinical chorioamnionitis, placental abruption, or fetal distress) with that of spontaneous preterm deliveries (PTDs) and to determine the effect of the latency period. STUDY DESIGN: The study group included women with PPROM at gestational age 28°(/)7-336(/)7 weeks (n = 488). Neonatal outcome was compared with a matched control group of women with spontaneous PTD (n = 1464). RESULTS: Neonates in the uncomplicated PPROM group were at increased risk for composite adverse outcome (53.7% vs 42.0%; P < .001), mortality (1.6% vs 0.0%; P < .001), respiratory morbidity (32.8% vs 26.4%; P = .006), necrotizing enterocolitis, jaundice, hypoglycemia, hypothermia, and polycythemia. Neonatal adverse outcome was more likely in cases of latency period >7 days, oligohydramnios, male fetus, and nulliparity. CONCLUSION: Consultation regarding prematurity-related morbidity in infants exposed to uncomplicated PPROM cannot be extrapolated from PTDs and should be stratified by the duration of the latency period and the other risk factors identified in the current study.

Perinatal outcome in pregnancies complicated by isolated oligohydramnios diagnosed before 37 weeks of gestation.

OBJECTIVE: To analyze pregnancy outcome in cases of isolated oligohydramnios at preterm. METHODS: A retrospective cohort study of singleton pregnancies diagnosed with isolated oligohydramnios at preterm (n = 108). Pregnancy outcome was compared with a matched control group of low-risk preterm pregnancies with normal levels of amniotic fluid in a 3:1 ratio (n = 324). RESULTS: Pregnancies complicated by isolated oligohydramnios were characterized by a higher rate of preterm deliveries (26.9% vs 12.3%, P < .001), most of which were iatrogenic, and a higher rate of labor induction and cesarean delivery. Neonates with isolated oligohydramnios were characterized by a lower birthweight and a higher rate of neonatal morbidity. These differences were eliminated when the analysis was limited to the subgroup of pregnancies with isolated oligohydramnios that were managed expectantly and delivered spontaneously at term. CONCLUSION: Adverse pregnancy outcome in cases of isolated oligohydramnios diagnosed at <37 weeks appears to be related to a considerable degree to iatrogenic prematurity.

Association of crown-rump length at 11 to 14 weeks' gestation and risk of a large-for-gestational-age neonate.

OBJECTIVE: The purpose of this study was to evaluate the association between crown-rump length (CRL) and the risk of a large-for-gestational-age (LGA) neonate. METHODS: Data were retrospectively collected on consecutive women with a healthy singleton pregnancy followed to delivery at our center from 2003 to 2006 who underwent nuchal translucency, pregnancy-associated plasma protein-A, and free beta-human chorionic gonadotropin screening at 11 to 14 weeks' gestation. Pregnancies were dated by the last menstrual period (LMP) confirmed by CRL at 6 to 10 weeks or the known time of fertilization. The fetal CRL at 11 to 14 weeks was obtained from frozen sonographic images. The measured CRL was converted to gestational weeks using the method of Hadlock et al (Radiology 1992; 182:501-505). The expected gestational age (GA) by the LMP was subtracted from the measured GA to yield the DeltaCRL. The association between the DeltaCRL and birth weight was statistically analyzed. RESULTS: The sample included 521 women. Fifty neonates (9.6%) were LGA (>or=90th percentile), 38 (7.3%) small for gestational age, and 433 (83.1%) appropriate for gestational age. The LGA group was characterized by significantly larger-than-expected CRL measurements (P = .033). The birth weight percentile and rate of LGA neonates were significantly higher in pregnancies in which the DeltaCRL was 1/2 week or greater (P = .007 and .033, respectively). There was a significant linear correlation between the DeltaCRL and birth weight percentile (P = .001). On multivariate logistic regression analysis, the DeltaCRL was the only significant predictor of an LGA neonate (odds ratio, 1.6; 95% confidence interval, 1.07-2.4; P = .023). CONCLUSIONS: Pregnancies with LGA neonates are characterized by larger-than-expected CRL measurements at 11 to 14 weeks' gestation.

Pregnancy outcome and mode of delivery after a previous operative vaginal delivery.

OBJECTIVE: : To assess pregnancy outcome and risk factors for repeat operative vaginal delivery in women with previous operative vaginal delivery. METHODS: : This was a case-control study of all nulliparous women who underwent operative vaginal delivery in a tertiary care medical center from 1993-2006 (n=4,153). The control group included nulliparous women who underwent spontaneous vaginal delivery during the same period in a 2:1 ratio (n=8,306). The women in each group who had a subsequent delivery at our center were identified (n=1,396 and n=2,591, respectively), and the outcome of the subsequent delivery was recorded. RESULTS: : Compared with the women in the spontaneous vaginal delivery group, women who underwent operative vaginal delivery in the index pregnancy had a higher rate of operative vaginal delivery (4.7% compared with 1.2%, P<.006) and cesarean delivery (8.5% compared with 4.6%, P<.001) in the subsequent pregnancy. The rate of neonatal birth injury (1.5% compared with 0.6%, P=.005) and third-degree or fourth-degree lacerations (0.7% compared with 0.2%, P=.01) was significantly higher in the group of women with a previous operative vaginal delivery. Risk factors for repeat operative vaginal delivery were as follows: failed vacuum extraction and prolonged second stage as the indication for operative vaginal delivery in the index pregnancy; prolonged interval (more than 3 years) between pregnancies; higher fetal weight, persistent occipitoposterior position, and use of epidural analgesia in the subsequent pregnancy. The presence of epidural analgesia in the index operative vaginal delivery was not associated with a decreased risk of repeat operative vaginal delivery. CONCLUSION: : Nulliparous women undergoing operative vaginal delivery are at increased risk of operative vaginal delivery and cesarean delivery in their subsequent pregnancy. Risk stratification based on the identified risk factors may assist clinicians in predicting the likelihood of repeat operative vaginal delivery and in counseling patients accordingly. LEVEL OF EVIDENCE: : II.

Hematologic Adverse Events Associated With Prolonged Valganciclovir Treatment in Congenital Cytomegalovirus Infection.

BACKGROUND: Valganciclovir (2/d) therapy for 6 months in neonates with symptomatic congenital cytomegalovirus (cCMV) infection improves hearing and neurodevelopmental outcome. The only reported adverse event was neutropenia. Since 2009, our protocol for symptomatic cCMV infection was a 1-year treatment of 2/d for the first 3 months followed by 9 months of 1/d. METHODS: A retrospective study. Infants with cCMV treated with valganciclovir for 1 year were recruited. Data of drug-related hematologic adverse events were collected. RESULTS: One hundred sixty infants were eligible; 46 (28.8%) had experienced at least 1 episode of neutropenia (58 episodes), the majority (39/46, 84.8%) during the first 3 months of treatment and 7 (15.2%) during the last 9 months of treatment. Grades 3 and 4 neutropenia occurred in 9 (5.6%) children, almost exclusively during the first 3 months of treatment. Anemia (hemoglobin <9 g/dL) was recorded in 12 (7.5%) children during the first 3 months of 2/d treatment. Four children presented with hemoglobin levels <7 g/dL and needed a blood transfusion. One child was diagnosed with transient pure red cell aplasia. No long-term adverse events were recorded. CONCLUSIONS: Although prolonged valganciclovir treatment for cCMV is safe, a close monitoring of the white blood cell count and hemoglobin levels is warranted. Much lower rates of grades 3 and 4 neutropenia were observed than previously reported, probably owing to our unique treatment protocol. Nevertheless, drug-induced anemia should be of primary concern. The optimal protocol assessing clinical outcome, concurrently with potential side effects, has not yet been determined.

Changes in the basic birth beliefs following the first birth experience: Self-fulfilling prophecies?

Women's basic beliefs about birth as a natural and as a medical process are associated with childbirth choices and experience. These beliefs have only recently been quantified and not much is known about their development. In the current study, we assessed the differential effects of the objective and the subjective birth experience on changes in these beliefs. Using self-report questionnaires, we evaluated prenatal to postpartum changes among 342 Israeli first-time mothers. Participants were recruited during pregnancy, between February 2016 and January 2017, mostly in clinical settings, and followed-up two months postpartum. On average, women's beliefs about birth being natural weakened following childbirth and their belief about birth being medical strengthened. In regression models, it was either the objective or the subjective experience that was related to change in the basic birth beliefs: A more medicalized birth was associated with strengthening of the medical belief while greater birth satisfaction was related to strengthening of the natural belief. A mediation effect was observed, which indicated that the beliefs are strengthened when the lived experience fulfilled women's expectation about birth being satisfying, natural or medical. This study adds to the growing body of knowledge regarding the development and evolution of the birth beliefs. It highlights the need to view the beliefs separately and to distinctively assess the objective and subjective birth experience. It supports the need to empower mothers, especially those who had more medicalized births or unsatisfactory ones, which would help conserve their belief in their body and in the normal physiological course of birth.

Congenital Cytomegalovirus Infection After a Multiple Birth Pregnancy.

BACKGROUND: Congenital cytomegalovirus (cCMV) infection is an important cause of hearing loss and neurodevelopment delay. While data on vertical transmission and neonatal outcome after singleton pregnancy with cCMV are well established, only scarce reports have addressed cCMV in multiple birth pregnancies. Furthermore, no studies have yet compared the outcome after birth and long-term follow-up of children with cCMV born after a singleton versus multiple pregnancies. METHODS: Infant outcome after birth of symptomatic versus asymptomatic infection was compared for infants born with cCMV after multiple (study group) and singleton (control group) pregnancies in a 1:2 ratio. RESULTS: Of 508 infants diagnosed with cCMV, 25 (4.9%) were born after a multiple pregnancy. Children in the study and control groups did not differ in terms of specific prenatal CMV investigations including amniocentesis and brain magnetic resonance imaging studies. However, prematurity rates were significantly higher in the study compared with control group (52% vs. 4%, P < 0.001). There was a higher rate of symptomatic cCMV infection in the study group than in the controls (48% vs. 14%, P < 0.001). Hearing impairment at birth was also more frequent in the study group (32% vs. 8%, P = 0.016). A long-term follow-up demonstrated that children in the study group had higher rates of neurologic sequelae (hearing impairment or neurodevelopmental delay) compared with children in the control group (20% vs. 4%, P = 0.016). CONCLUSIONS: Infants with cCMV born after multiple birth pregnancies are born earlier and have a higher risk of symptomatic disease at birth and worse long-term neurologic outcome than those born after a singleton pregnancy. This important group of children warrants meticulous prenatal and postnatal care.